Thought provoking findings by #TheRyanGroup in preprint today showing T cell suppression in the tumour microenvironment via stromal cell sialylation is one of the most discussed/tweeted journal articles in Multiple Myeloma this week.
Very happy to have been involved in this work led by @aideenryan1 Identifies for the first time an important role for sialylation of stromal cells in promoting immune suppression in cancer. #glycotime #Immunotherapy #cancer #Checkpoint #siglec #sialyation https://t.co/XB6MQ3M32a
— Michael O’Dwyer (@MichaelodwyerMD) June 19, 2021
Stromal cell sialylation suppresses T cells in inflammatory tumour microenvironments: A new tumour stromal cell immune checkpoint?
https://www.biorxiv.org/content/10.1101/2021.06.18.447879v1
Abstract
Immunosuppressive tumour microenvironments (TME) reduce the effectiveness of immune responses in cancer. Non-haematopoietic mesenchymal stromal cells (MSC), the precursor to cancer associated fibroblasts (CAFs), dictate tumour progression by enhancing immune cell suppression. Hyper-sialylation of glycans promotes immune evasion in cancer, but the role of sialyation in stromal cell-mediated immunosuppression is unknown. Here we study changes in sialyltransferase (ST) enzymes and associated surface expressed sialic acid in stromal cells following inflammatory and tumour secretome conditioning. We show that tumour conditioned stromal cells have increased levels of sialyltransferases, α2,3/6 linked sialic acid and siglec ligands. In tumour models of solid (colorectal cancer) and haematological (multiple myeloma) stromal rich tumours, stromal cell sialylation is associated with enhanced immunosuppression. Using datasets and patient samples, we confirm that targeting sialylation in tumour stromal cells reverses immune cell exhaustion. Targeting stromal cell sialylation may represent a novel immune checkpoint to reactivate anti-tumour immunity.